Study on Combined Vaccination With SARS-CoV-2 Inactivated Vaccine and Quadrivalent Influenza Vaccine

A Study to Evaluate the Safety and Immunogenicity of Concomitant Administration of the SARS-CoV-2 Inactivated Vaccine (Vero Cell) With Quadrivalent Influenza Vaccine in Adults Aged From 18 to 59 Years

This study is an open-label, single-center, randomized phase IV clinical trial of the SARS-CoV-2 inactivated vaccine manufactured by Sinovac Research & Development Co., Ltd. The purpose of this study is to evaluate the safety and immunogenicity of concomitant administration of the SARS-CoV-2 Inactivated Vaccine (Vero cell) with Quadrivalent Influenza Vaccine in adults aged from 18 to 59 Years

Study Overview

• Status: Completed
• Conditions: COVID-19; Influenza
• Intervention / Treatment: Biological: Two doses of inactivated SARS-CoV-2 vaccine at the schedule of day 0,28 and one dose Quadrivalent Influenza Vaccine on day 0 or day 28.; Biological: Two doses of inactivated SARS-CoV-2 vaccine at the schedule of day 0,28 and one dose Quadrivalent Influenza Vaccine on day 14.

Detailed Description

This study is an open-label, single-center, randomized phase IV clinical trial of the SARS-CoV-2 inactivated vaccine (Vero cell) manufactured by Sinovac Research & Development Co., Ltd. The purpose of this study is to evaluate the safety and immunogenicity of concomitant administration of the SARS-CoV-2 Inactivated Vaccine (Vero cell) with Quadrivalent Influenza Vaccine in adults aged from 18 to 59 Years. 480 healthy adults as participants are randomly assigned into two groups in the ratio 1:1. The first group was the combined immunization group, which is randomly divided into two subgroups, 120 subjects in each group. The combined immunization subgroup Ⅰ receive SARS-CoV-2 inactivated vaccine &Quadrivalent Influenza Vaccine on day 0 and SARS-CoV-2 inactivated vaccine (second dose) on day 28.The combined immunization subgroup Ⅱ receive SARS-CoV-2 inactivated vaccine on day 0 and SARS-CoV-2 inactivated vaccine (second dose) & Quadrivalent Influenza Vaccine on day 28. The second group was the non combined immunization group，which receive SARS-CoV-2 inactivated vaccine (first dose) on day 0, Quadrivalent Influenza Vaccine on day 14 and SARS-CoV-2 inactivated vaccine (second dose) on day 28.

• Study Type: Interventional
• Enrollment (Actual): 480
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Quzhou, Zhejiang, China, 324300
      • Kaihua County Center for Disease Control and Prevention

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 59 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy adults aged 18-59 years;
• The subject can understand and voluntarily sign the informed consent form;
• Proven legal identity

Exclusion Criteria:

• Travel history / residence history of communities with case reports within 14 days;
• History of contact with a SARS-CoV-2 infection (positive in nucleic acid test) within 14 days;
• Have contacted patients with fever or respiratory symptoms from communities with case reports within 14 days;
• Two or more cases of fever and / or respiratory symptoms in a small contact area of volunteers, such as home, office etc. within 14 days;
• History of SARS-CoV-2 infection;
• History of asthma, history of allergy to the vaccine or vaccine components, or serious adverse reactions to the vaccine, such as urticaria, dyspnea, and angioedema;
• Congenital malformations or developmental disorders, genetic defects, severe malnutrition, etc.;
• Autoimmune disease or immunodeficiency / immunosuppression;
• Severe chronic diseases, severe cardiovascular diseases, hypertension and diabetes that cannot be controlled by drugs, liver or kidney diseases, malignant tumors, etc.;
• Severe neurological disease (epilepsy, convulsions or convulsions) or mental illness;
• Thyroid disease or history of thyroidectomy, spleenlessness, functional spleenlessness, spleenlessness or splenectomy resulting from any condition;
• Diagnosed abnormal blood coagulation function (eg, lack of blood coagulation factors, blood coagulopathy, abnormal platelets) or obvious bruising or blood coagulation;
• Immunosuppressive therapy, cytotoxic therapy, inhaled corticosteroids (excluding allergic rhinitis corticosteroid spray therapy, acute noncomplicated dermatitis superficial corticosteroid therapy) in the past 6 months;

• Physical examination has clinically significant abnormal hematology and biochemistry laboratory test results that exceed the reference value range (only applicable to phase I clinical trials):

  1. Blood routine test: white blood cell count, hemoglobin, platelet count;
  2. Detection of blood biochemical indicators: alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), creatinine (CR), fasting blood glucose;
  3. Urine routine index: urine protein (PRO);
• History of alcohol or drug abuse;
• Receipt of blood products within in the past 3 months;
• Receipt of other investigational drugs in the past 30 days;
• Receipt of attenuated live vaccines in the past 14 days;
• Receipt of inactivated or subunit vaccines in the past 7 days;
• Acute diseases or acute exacerbation of chronic diseases in the past 7 days;
• Axillary temperature >37.0°C;
• Already pregnant (including a positive urine pregnancy test) or are breastfeeding, planning to get pregnant within 3 months;
• According to the investigator's judgment, the subject has any other factors that are not suitable for participating in the clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Combined immunization group; The combined immunization group is randomly divided into two subgroups, 120 subjects in each group. The combined immunization subgroup Ⅰ receive SARS-CoV-2 inactivated vaccine (Vero cell)&Quadrivalent Influenza Vaccine on day0 and SARS-CoV-2 inactivated vaccine (Vero cell) (second dose) on day 28.The combined immunization subgroup Ⅱ receive SARS-CoV-2 inactivated vaccine (Vero cell) on day 0 and SARS-CoV-2 inactivated vaccine (Vero cell) (second dose) & Quadrivalent Influenza Vaccine on day 28.	Biological: Two doses of inactivated SARS-CoV-2 vaccine at the schedule of day 0,28 and one dose Quadrivalent Influenza Vaccine on day 0 or day 28.; The inactivated SARS-CoV-2 vaccine was manufactured by Sinovac Research & Development Co., Ltd., with a antigen content of 600SU/0.5ml. The Quadrivalent Influenza Vaccine manufactured by Sinovac Biotech Co.,Ltd. including 4 antigens H1N1, H3N2, BV and BY, 15μg for each, 0.5ml per dose.
Experimental: Non combined immunization group; The non combined immunization group receive SARS-CoV-2 inactivated vaccine (Vero cell)(first dose) on day 0, Quadrivalent Influenza Vaccine on day 14 and SARS-CoV-2 inactivated vaccine (Vero cell)(second dose) on day 28.	Biological: Two doses of inactivated SARS-CoV-2 vaccine at the schedule of day 0,28 and one dose Quadrivalent Influenza Vaccine on day 14.; The inactivated SARS-CoV-2 vaccine was manufactured by Sinovac Research & Development Co., Ltd., with a antigen content of 600SU/0.5ml. The Quadrivalent Influenza Vaccine manufactured by Sinovac Biotech Co.,Ltd. including 4 antigens H1N1, H3N2, BV and BY, 15μg for each, 0.5ml per dose.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety index-incidence of adverse reactions within 7 days after each dose	Incidence of adverse reactions within 7 days after each dose	Day 0-7 after each dose vaccination
Immunogenicity index-seroconversion rates of neutralizing antibody against SARS-CoV-2	Neutralizing antibody assay will be performed using the micro-neutralization method. Seroconversion will be defined as a change from seronegative (<1:8) to seropositive (≥1:8), or ≥4 fold increase from baseline.	The 28th day after the second dose vaccination of the inactivated SARS-CoV-2 vaccine

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety index-incidence of adverse reactions within 56 days after the first dose vaccination	Incidence of adverse reactions within 56 days after the first dose vaccination	Day 0-56 after the first dose vaccination
Safety index-incidence of serious adverse events	SAE will be collected throughout the clinical trial.	Day 0-56 after the first dose vaccination
Immunogenicity index-seropositive rates of neutralizing antibody against SARS-CoV-2	Neutralizing antibody assay will be performed using the micro-neutralization method, and subjects with a antibody titer ≥1:8 will defined as seropositive.	The 28th day after each dose vaccination
Immunogenicity index-geometric mean titer (GMT) of neutralizing antibody against SARS-CoV-2	Neutralizing antibody assay will be performed using the micro-neutralization method.	The 28th day after each dose vaccination
Immunogenicity index-geometric mean ratio (GMR) of neutralizing antibody against SARS-CoV-2	Neutralizing antibody assay will be performed using the micro-neutralization method. Ratio of post-vaccination titer divided by baseline titer will be calculated.	The 28th day after each dose vaccination
Immunogenicity index-seroconversion rates of influenza HI antibodies	Seroconversion will be defined as a change from seronegative (<1:10) to protective (≥1:40), or ≥4 fold increase from baseline(≥1:10).	The 28th day after the vaccination
Immunogenicity index-protective rates of influenza HI antibodies	The standard of reaching the protective rate is that the antibody titer ≥1:40.	The 28th day after the vaccination
Immunogenicity index-geometric mean titer (GMT) of influenza HI antibodies	influenza HI antibodies assay will be performed using the micro hemagglutination inhibition test	The 28th day after the vaccination
Immunogenicity index-geometric mean ratio (GMR) of influenza HI antibodies	influenza HI antibodies assay will be performed using the micro hemagglutination inhibition test	The 28th day after the vaccination

Collaborators and Investigators

• Sponsor: Sinovac Research and Development Co., Ltd.
• Investigators: Principal Investigator: Huakun Lv, Master, Zhejiang Provincial Center for Disease Control and Prevention

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2021
• Primary Completion (Actual): May 28, 2021
• Study Completion (Actual): May 28, 2021

Study Registration Dates

• First Submitted: March 15, 2021
• First Submitted That Met QC Criteria: March 15, 2021
• First Posted (Actual): March 17, 2021

Study Record Updates

• Last Update Posted (Actual): July 26, 2021
• Last Update Submitted That Met QC Criteria: July 23, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: PRO-QINF-4001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No